Metabolic Network Reconstruction of Treponema Pallidum Spp. Pallidum

Background: Since the discovery, made in 1905 by Schaudinn and Hoffmann, of Treponema pallidum ssp. pallidum as the etiologic agent of syphilis, medicine has made significant progress against this disease. Yet, despite the availability of diagnostic tests and a therapy based on antibiotics, the world has not stopped being burdened by syphilis, that has been re-emerging globally over the last few decades (WHO Report, 2008), for which no vaccine is still available and which, moreover, in its early stages enhances the transmission of HIV. Continuous in vitro culture of this organism has still not been achieved, imposing a substantial roadblock to its experimental inspection, and even the sequencing of its genome (Fraser et al., 1998) did not yield an obvious solution to the cultivation problem. While much has already been tried on the laboratory bench, this pathogen has still not (to our knowledge) been tackled using a systems biology approach.

Results: Here, we present a first manually curated draft reconstruction of the metabolic network in Treponema pallidum ssp. pallidum towards a genome-scale metabolic model (GEM). At this time, the model iSM161 comprises 161 genes of 1,039 predicted open reading frames that are responsible for 239 reactions of 277 metabolites. The model is still under development and steadily updated. For the reconstruction, COBRApy has been used, where subsystem information is added and parsed as SBML groups extension using libSBML.

Discussion: Using this reconstruction, together with the application of COBRA methods, we anticipate to gather new insights into the pathogen’s physiology and pathology, and in how this spirochete, which has earned the designation of “stealth pathogen,” succeeds in making a living and eluding human’s immune defenses as well as cultivation attempts. It is planned to make the model available to the community in SBML format.